Kir2.2 channels
| Channel name | Kir2.2 |
| Description | Inwardly rectifying potassium channel Kir2.2 subunit |
| Other names | IRK2, RB-IRK2, MB-IRK2, hIRK |
| Molecular information | Human (KCNJ12): 427aa, Locus ID: 3768, GenBank: L36069, NM_021012, PMID: 7859381,1 chr. 17p11.12 |
| Rat (Kcnj12): 427aa, Locus ID: 117052, GenBank: X78461, NM_053981, PMID: 8137958,3 chr. 10q22 | |
| Mouse (Kcnj12): 427aa, Locus ID: 16515, GenBank: X80417, NM_010603, PMID: 8083233,4 chr. 11, 34.15 centimorgans | |
| Drosophila melanogaster: GenBank: NM_170076, PMID: 10731132,5 chr. 95A1-95A1 | |
| Associated subunits | Kir2.1 and Kir2.3 to form heteromeric channel, auxiliary subunit: SAP97, Veli-1, Veli-3,6 PSD-95, Chapsyn-110, SAP102, CASK, Dlg2, Dlg3, Pals2, actin-binding LIM protein, α1, β1, and β2 syntrophin, dystrophin, Dp71, α-dystrobrevin-1, and α-dystrobrevin-27 |
| Functional assays | Voltage-clamp |
| Current | IK1 in the heart with other Kir2 subunits |
| Conductance | 34.2pS (Kir2.2 homomeric channel) in 140 mM symmetric K+4 |
| 30.0pS (Kir2.2—Kir2.1 concatemer) in 145 mM symmetric K+8 | |
| 30.1pS (Kir2.1—Kir2.2 concatemer) in 145 mM symmetric K+8 | |
| Ion selectivity | K+ |
| Activation | Voltages negative to EK,3 intercellular alkalization, pK = 6.29 |
| Inactivation | Voltages positive to EK,3 intercellular acidification, pK = 6.29 |
| Activators | Not established |
| Gating inhibitors | Not established |
| Blockers | Ba2+ (IC50 to Kir2.2 homomeric channel, 0.5 μM; to Kir2.1/Kir2.2 heteromeric channel, 0.64 μM; to either Kir2.1—Kir2.2 or Kir2.2—Kir2.1 concatemer, 0.68 μM; to either Kir2.2—Kir2.3 or Kir2.3—Kir2.2 concatemer, 1.73 μM; to Kir2.2/Kir2.3 heteromeric channel, 1.94 μM,8 intracellular Mg2+ (Ki = 11 μM10), intracellular polyamines (IC50 for spermine, 3 nM10) |
| Radioligands | None |
| Channel distribution | Cerebellum, skeletal muscle, kidney, heart, forebrain |
| Physiological functions | Maintenance of a resting membrane potential, repolarization of cardiac action potential, modulation of cell excitability |
| Mutations and pathophysiology | Kir2.2 knockout mice show 50% reduction in IK1, and Kir2.1 knockout mice lack a detectable IK1 at 4 mM external K+, suggesting that a large population of Kir2.2 behaves as a heteromeric channel with Kir2.1 to form IK111 |
| Pharmacological significance | Not established |
aa, amino acids; chr., chromosome.
↵1. Wible BA, De Biasi M, Majumder K, Taglialatela M, and Brown AM (1995) Cloning and functional expression of an inwardly rectifying K+ channel from human atrium. Circ Res 76:343-350
↵2. Hugnot JP, Pedeutour F, Le Calvez C, Grosgeorge J, Passage E, Fontes M, and Lazdunski M (1997) The human inward rectifying K+ channel Kir 2.2 (KCNJ12) gene: gene structure, assignment to chromosome 17p11.1, and identification of a simple tandem repeat polymorphism. Genomics 39:113-116
↵3. Koyama H, Morishige K, Takahashi N, Zanelli J, Fass DN, and Kurachi Y (1994) Molecular cloning functional expression and localization of a novel inward rectifier potassium channel in the rat brain. FEBS Lett 341:303-307
↵4. Takahashi N, Morishige K, Jahangir A, Yamada M, Findlay I, Koyama H, and Kurachi Y (1994) Molecular cloning and functional expression of cDNA encoding a second class of inward rectifier potassium channel. J Biol Chem 269:23274-23279
↵5. Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer SE, Li PW, Hoskins RA, Galle RF, et al (2000) The genome sequence of Drosophila melanogaster. Science 287:2185-2195
↵6. Leonoudakis D, Conti LR, Radeke CM, McGuire LMM, and Vandenberg CA (2004) A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. J Biol Chem 279:19051-19063
↵7. Leonoudakis D, Conti LR, Anderson S, Radeke CM, McGuire LMM, Adams ME, Froehner SC, Yates III JR, and Vandenberg CA (2004) Protein trafficking and anchoring complexes revealed by proteomic analysis of inward rectifier potassium channel (Kir2x)-associated proteins. J Biol Chem 279:22331-22346
↵8. Preisig-Müller R, Schlichthörl G, Goerge T, Heinen S, Brüggemann A, Rajan S, Derst C, Veh R, and Daut J (2002) Heteromerization of Kir2x potassium channels contributes to the phenotype of Andersen's syndrome. Proc Natl Acad Sci USA 99:7774-7779
↵9. Collins A and Larson M (2002) Differential sensitivity of inward rectifier K+ channels to metabolic inhibitors. J Biol Chem 277:35815-35818
↵10. Yamashita T, Horio Y, Yamada M, Takahashi N, Kondo C, and Kurachi Y (1996) Competition between Mg2+ and spermine for a cloned IRK 2 channel expressed in a human cell line. J Physiol 493:143-156
↵11. Zaritsky JJ, Redell JB, Tempel BL, and Schwarz TL (2001) The consequences of disrupting cardiac inwardly rectifying K+ current (IK1) as revealed by the targeted deletion of the murine Kir2.1 and Kir2.2 genes. J Physiol 533:697-710